The role of early immunotherapy in rasmussen's encephalitis

Rasmussen's Encephalitis (RE) is a rare clinical syndrome of chronic progressive unihemispheric cortical inflammation and atrophy, with explosive focal onset seizures which are commonly intractable and may include epilepsia partialis continua (EPC), unilateral neurologic deficits, and cognitive decline. Despite awareness of this disease since characterization in 1958, the underlying pathogenesis of RE remains unknown. Neurosurgical intervention, via functional hemispherectomy of the affected cerebral hemisphere, remains the standard of care for RE. However, due to the invasive nature of this procedure, and emerging evidence for a neuroinflammatory pathogenesis, various immunologic mechanisms have been proposed and immunotherapies trialed for patients with RE. The rare nature of the condition and heterogenous data in the literature have made determination of the role of immunotherapies, such as rituximab, difficult to ascertain. Here we report a series of three patients with pediatric RE, all of whom received early administration of immunotherapy in the context of restricted oligoclonal bands in the cerebrospinal fluid. While two patients were non-responders, one patient exhibited no radiographic progression on rituximab and one of those patients had clinical improvement. We discuss the potential role and mechanism of rituximab as well as the proposed mechanisms and available data for immunotherapy in RE more broadly. Although data remains limited, biomarkers of immunologic dysregulation may serve as indications for the use of immunotherapy in individuals with RE. Further, selection of immunotherapy, guided by ancillary testing including CSF analysis, may serve as an adjunct to hemispherectomy and neurosurgical intervention in some patients.